Slide source www Female Sexual Dysfunction Online org

Slide source: www. Female. Sexual. Dysfunction. Online. org

Testosterone Therapy for Hypoactive Sexual Desire Disorder Slide source: www. Female. Sexual. Dysfunction. Online. org

Introduction § Rationale for use § Combination estrogen-testosterone therapy § Testosterone use in women – Therapies available and under investigation – Dosing/administration issues – Clinical trials of testosterone use in women – Managing side effects § Patient selection Slide source: www. Female. Sexual. Dysfunction. Online. org

Rationale for Testosterone Therapy § Testosterone levels in women decline with aging – Women in their 40 s have approximately one-half the level of women in their 20 s § Women who undergo oophorectomy experience dramatic decreases in the level of testosterone – Level of testosterone decreases to one half of those prior to surgery Zumoff B, et al. J Clin Endocrinol Metab. 1995; 80: 1429 -1430. Judd HL, et al. J Clin Endocrinol Metab. 1974; 39: 1020 -1024. Slide source: www. Female. Sexual. Dysfunction. Online. org

Rationale for Testosterone Therapy (cont’d) § Testosterone has been linked to sexual desire and coital frequency in menopausal women § Accumulating data indicate that testosterone therapy increases sexual function, including sexual desire, in postmenopausal women Mc. Coy NL, et al. Maturitas. 1985; 7: 203 -210. Shifren JL, et al. N Engl J Med. 2000; 343: 682 -688. Lobo RA, et al. Fertil Steril. 2003; 79: 1341 -1352. Slide source: www. Female. Sexual. Dysfunction. Online. org

Combination Estrogen. Testosterone Therapy Slide source: www. Female. Sexual. Dysfunction. Online. org

Impact of Estrogen Deficiency on Sexual Function § Changes in urogenital anatomy – Shortening and loss of elasticity of the vagina – Diminished secretions – Increased p. H – Thinning of vaginal epithelial layers § Reduced blood flow § Reduced nerve transmission and discharge § Sleep disruption § Mood alterations Sarrel PM. Obstet Gynecol. 1990; 75: 26 S-30 S. Bachmann GA, et al. Menopause. 2004; 11: 120 -130. Slide source: www. Female. Sexual. Dysfunction. Online. org

Percentage of Women Reporting Problems Low Estrogen Is Associated With Increased Prevalence of Sexual Problems N=93; significance not reported. Sarrel PM. J Womens Health Gend Based Med. 2000; 9: S 25 -S 32. Sarrel PM. Obstet Gynecol. 1990; 75: 26 S-30 S. Slide source: www. Female. Sexual. Dysfunction. Online. org

Efecto de Terapia con Estrógenos and Estrógenos. Andrógenos sobre Síntomas menopaúsicos Placebo Low-Dose High-Dose EE EE EE + MT * * * * Postplacebo run-in period Month 1 Month 3 N=93; *P≤ 0. 05 EE=esterified estrogens; MT=methyltestosterone Simon J, et al. Menopause. 1999; 6: 138 -146. Slide source: www. Female. Sexual. Dysfunction. Online. org

Testosterone Use in Women Slide source: www. Female. Sexual. Dysfunction. Online. org

Testosterone Therapies Available and Under Investigation* § Oral § Transdermal – Methyltestosterone – Transdermal testosterone – Testosterone undecanoate patch – Testosterone gel § Intramuscular – Testosterone propionate – Testosterone cypionate – Testosterone enanthate § Subcutaneous (implant) – Testosterone propionate pellets – Testosterone crystalline pellets – Testosterone emulsion – Testosterone spray § Other – Testosterone-containing vaginal ring – Sublingual testosterone in propylene glycol * Not approved by US Food and Drug Administration for use in women. Slide source: www. Female. Sexual. Dysfunction. Online. org

Niveles medios de Deseo Sexual Estrógenos y Enantato de Testosterona: Deseo sexual 5 Estrógeno + TE Control Inyeccion 4 3 2 1 0 B 1 2 3 Semanas 4 N=65; TE=testosterona enantato Sherwin BB, et al. Psychosom Med. 1987; 49: 397 -409. Slide source: www. Female. Sexual. Dysfunction. Online. org

Estradiol and Testosterone Implants: Sexual Function Summary Statistics Libido Estrogen + testosterone Activity Satisfaction Pleasure Fantasy Orgasm Relevancy 5 N=34 6 7 8 9 10 Sexuality Score (Means of 6, 12, 18, and 24 Months) Davis SR, et al. Maturitas. 1995; 21: 227 -236. Slide source: www. Female. Sexual. Dysfunction. Online. org

Estrogen and Methyltestosterone: Effect on Testosterone Levels EE EE+MT N = 111 N = 107 Baseline 20. 8 1. 1 18. 9 8. 4 Change from baseline (mean serum concentration) -0. 1 7. 4 -3. 7 6. 8 Baseline 3. 1 2. 7 1. 5 Change from baseline (mean serum concentration) -0. 3 2. 4 2. 0 Treatment difference Total Testosterone (ng/d. L) P=0. 02 Bioavailable Testosterone (pg/m. L) P<0. 010 EE=esterified estrogens; MT=methyltestosterone Lobo RA, et al. Fertil Steril. 2003; 79: 1341 -1352. Slide source: www. Female. Sexual. Dysfunction. Online. org

Estrogen and Methyltestosterone: Sexual Desire Mean Change 0. 9 * EE (n = 111) 0. 6 EE+MT (n = 107) 0. 3 0 4 8 12 16 Study Week *P<0. 02 vs baseline EE=esterified estrogens; MT=methyltestosterone Lobo RA, et al. Fertil Steril. 2003; 79: 1341 -1352. Slide source: www. Female. Sexual. Dysfunction. Online. org

Estrogen and Methyltestosterone: Frequency of Interest/Desire † † EE (n = 111) EE+MT (n = 107) * Study Week *P<0. 02 vs baseline; †P<0. 01 vs baseline EE=esterified estrogens; MT=methyltestosterone Lobo RA, et al. Fertil Steril. 2003; 79: 1341 -1352. Slide source: www. Female. Sexual. Dysfunction. Online. org

Estrogen and Methyltestosterone: Sexual Functioning Change in Raw Score From Previous Hormone Therapy 3. 5 3 EE EE+MT * 2. 5 2 * 1. 5 † 1 0. 5 0 -0. 5 Sensation Desire Frequency Vaginal Changes and Desire N=20; *P<0. 01; †P≤ 0. 05 EE=esterified estrogens; MT=methyltestosterone Sarrel PM, et al. J Reprod Med. 1998; 43: 847 -856. Slide source: www. Female. Sexual. Dysfunction. Online. org

Estrogen and Testosterone Patch: Free and Bioavailable Testosterone Levels Placebo Baseline 150 mcg 14 * Free T (pg/m. L) 7 6 5 * 4 3 2 1 0 Regimen (+CEE) Bioavailable T (ng/d. L) 8 300 mcg * 12 10 8 * 6 4 2 0 CEE=conjugated equine estrogens; T=testosterone Endocrine Sciences normal range for cycling women Regimen (+CEE) N=75; *P<0. 001 for comparison with placebo Shifren JL, et al. N Engl J Med. 2000; 343: 682 -688. Slide source: www. Female. Sexual. Dysfunction. Online. org

Oral Estrogen and Testosterone Patch: Sexual Function 120 Baseline 150 mcg Placebo 300 mcg Percentage of Normative Mean 110 100 * 90 80 * 70 60 50 40 Thoughts/ Desires Arousal Frequency Pleasure/ Orgasm Problems N=75; *P<0. 05 for comparison with placebo Shifren JL, et al. N Engl J Med. 2000; 343: 682 -688. Slide source: www. Female. Sexual. Dysfunction. Online. org

Oral Estrogen and Testosterone Patch: Effect on Sexual Function Author (Year) Population (N) Treatment (Dose) Outcome (at 24 Weeks) Braunstein (2003) SM, HSDD (N=447) T patch (150, 300, 450 mcg/d) Placebo patch Desire Activity Davis (2003) SM, HSDD (N=77) T patch (300 mcg/d) Placebo patch Desire Activity SM=surgically menopausal; HSDD=hypoactive sexual desire disorder; T=testosterone Braunstein GD, et al. In: Program and abstracts of the 14 th annual meeting of the North American Menopause Society; September 17 -20, 2003; Miami Beach, Fla. Abstract 60. Davis S, et al. Fertil Steril. 2003; 80(suppl 3): 76. Slide source: www. Female. Sexual. Dysfunction. Online. org

Oral Estrogen and Testosterone Patch: Effect on Sexual Function (cont’d) Author (Year) Population (N) Treatment (Dose) Outcome (at 24 Weeks) Simon (2004) SM, HSDD (N=562) T patch (300 mcg/d) Placebo patch Desire Activity Buster (2004) SM, HSDD (N=533) T patch (300 mcg/d) Placebo patch Desire Activity SM=surgically menopausal; HSDD=hypoactive sexual desire disorder; T=testosterone Simon JA, et al. Obstet Gynecol. 2004; 103(suppl): 64 S. Buster J, et al. In: Program and abstracts of the 86 th annual meeting of the Endocrine Society; June 1619, 2004; New Orleans, La. Abstract OR 44 -6. Slide source: www. Female. Sexual. Dysfunction. Online. org

Estrogen and Testosterone Undecanoate: Sexual Function Baseline Mc. Coy Sex Scale Score (Mean) * EV * * Enjoyment of Sex Satisfaction With Frequency of Sex EV + TU Interest in Sex *P<0. 05 vs EV at 24 weeks N=50; EV-estradiol valerate; TU-testosterone undecanoate Floter A, et al. Climacteric. 2002; 5: 357 -65. Slide source: www. Female. Sexual. Dysfunction. Online. org

Potential Side Effects With Testosterone Therapies § Hirsutism § Acne § Voice deepening § Alopecia § Liver toxicity § Negative effects on lipoproteins § Clitoromegaly Slide source: www. Female. Sexual. Dysfunction. Online. org

Side Effects in Studies With Testosterone Therapies § Few side effects are reported in studies § Increased doses are associated with – Facial hair – Acne/oily skin § Oral preparations – Decreases in high-density lipoprotein • Not seen with transdermal preparations Slide source: www. Female. Sexual. Dysfunction. Online. org

Estrogen and Testosterone Patch: Safety Mean Score (SEM) 2. 5 Placebo Baseline 150 mcg 300 mcg * 2. 0 1. 5 1. 0 0. 5 0. 0 Hirsutism Acne Facial Depilation (Lorenzo Scale) (Palatsi Scale) (Times/Month) N=75; *P<0. 05 for comparison with placebo Shifren JL, et al. N Engl J Med. 2000; 343: 682 -688. Slide source: www. Female. Sexual. Dysfunction. Online. org

Estrogen and Methyltestosterone: Safety EE EE+MT Baseline score 2. 3 2. 5 2. 9 3. 3 Change from baseline at week 16 0. 0 1. 9 -0. 4 2. 2 Baseline score 0. 1 0. 4 0. 2 0. 5 Change from baseline at week 16 0. 2 0. 5 0. 1 0. 5 Hirsutism score (Lorenzo scale) Acne score (Palatsi scale) EE=esterified estrogens; MT=methyltestosterone Lobo RA, et al. Fertil Steril. 2003; 79: 1341 -1352. Slide source: www. Female. Sexual. Dysfunction. Online. org

Patient Selection § Testosterone therapy, in conjunction with estrogen therapy, may be indicated in women with: – Surgical menopause – Decreased libido – Diminished sense of well-being Slide source: www. Female. Sexual. Dysfunction. Online. org